The lymphatic system consists of different lymphoid organs (thymus, bone marrow, spleen, lymph nodes, tonsils, appendix, Peyer's patches), a conducting network of lymphatic vessels, and the circulating lymph fluid. Within the body, the lymphatic system fulfills important functions in the removal of interstitial fluid from tissues, the absorption and transport of fatty acids and fats as chyle from the digestive system, or the stimulation of immune responses through antigen-presenting cells (APCs), such as dendritic cells, in the lymph nodes.
The human body comprises altogether between five and six hundred lymph nodes located at intervals along the lymphatic vessels. Many of these lymph nodes are grouped in clusters in different body regions, for example in the underarm and abdominal areas. Lymph nodes are particularly numerous in the mediastinum in the chest, neck, pelvis, axilla (armpit), inguinal (groin) region, and in association with the blood vessels of the intestines. One of their important functions is to filter the interstitial fluid (lymph) of the body region where they are located and to transport the filtered fluid to the blood.
The lymph node is surrounded by a capsule of connective tissue which includes smooth muscle cells, thus allowing the lymph node to contract and to advance the lymph fluid. The core of the lymph node consists of an organized collection of lymphoid tissue formed by a meshwork of reticular cells and fibers with embedded lymph follicles, spherical aggregations of lymphocytes in the meshwork of the reticulum.
Numerous small afferent lymph vessels enter through the capsule of the lymph node, whereas only a single efferent lymph vessel leaves the capsule. The afferent lymph vessels transport lymph to the core of the lymph node, where the lymph is filtered and then drained out by the efferent lymph vessel in order to be returned to the blood. The efferent lymph vessel leaves the capsule at the “hilum”, a depression on the surface of the lymph node, which makes the otherwise spherical lymph node, bean-shaped or ovoid. In addition to the efferent lymph vessel, the arteries and veins supplying the lymph node with blood enter and exit at the hilum region.
There are two different types of vessels among the lymph vessels, capillaries and collectors. In contrast to capillaries, collectors are surrounded by smooth muscle cells and include valves, thus ensuring contractile, unidirectional transport of lymph fluid.
If lymph nodes are unable to fulfill their function, this may give rise to lymphedema, a condition characterized by the swelling of body tissue due to the accumulation of lymph fluid in the interstitium. Lymphedema usually affects limbs, though the face, neck and abdomen may also be affected. In extreme cases, lymphedema may even result in an abnormal enlargement of certain body parts (elephantiasis).
Lymphedema often becomes chronic. Frequently, lymphedema is caused by severe infection, in particular by parasitic diseases, such as lymphatic filariasis, or arises as a side effect of cancer therapy (e.g. due to surgical removal of cancerous lymph nodes in the armpit, causing the atm to swell due to poor lymphatic drainage, or groin, causing swelling of the leg, or due to radiotherapy).
At present, no standard curative treatment is available for lymphedema patients, as current practice involves symptomatic care only. Typically, patients are treated by compression garments or massages (lymph drainage). While temporarily reducing the volume of edema by pressing lymph from the edema into body regions with a functioning lymph system, such treatment options only target the symptoms of lymphedema and thus their effects are only transitory.
A generally accepted etiologic surgical standard therapy for the treatment of lymphedema does not exist yet. In recent years, significant success has been reported by an approach in which a lymph node from an unaffected region of the patient's body is transplanted to the body part affected by lymphedema. In this procedure, a lymph node package (lymph node and fat tissue) is removed from the axillary or inguinal region and is transplanted by microsurgical methods to the area affected by lymphedema (Becker et al., 2006). The lymph node's blood supply vessel is connected surgically under the microscope to a recipient vessel in the area of lymphedema, thus ensuring survival of the transplanted lymph node. The surviving lymph node apparently secretes growth factors (VEGF-C) which locally induce formation of new lymph vessels. The transplanted lymph node with newly formed lymph vessels improves the removal of lymph fluid from the affected area, thus causing a significant reduction in the swelling of the affected tissue.
Due to the high demands of the microsurgical procedure, however, this type of operation to transplant a lymph node is an extended surgical intervention of 5-8 hours under general anesthesia which typically involves hospitalization of the patient for at least 5-7 days. Moreover, due to the significant risks of such a major surgical intervention, it is difficult to reduce the morbidity associated with this treatment option. Therefore, this approach for the treatment of lymphedema involves high costs as well as significant strain, hassle and risks for the patient.
In the literature, avascular transplantation of autologous lymph node fragments has been reported (Sommer et al., 2012; Pabst et al., 1988). However, the handling and fixation of small lymph node fragments in the target tissue (typically by suture) is difficult and time-consuming. Moreover, the size of the lymph nodes obtained by such techniques is rather small, there is little influence on the size and shape of the resulting lymph nodes and the success rate is dissatisfactory.